More than a feeling: A unified view of stress measurement for population science.

Stress can influence health throughout the lifespan, yet there is little agreement about what types and aspects of stress matter most for human health and disease. This is in part because "stress" is not a monolithic concept but rather, an emergent process that involves interactions between individual and environmental factors, historical and current events, allostatic states, and psychological and physiological reactivity. Many of these processes alone have been labeled as "stress." Stress science would be further advanced if researchers adopted a common conceptual model that incorporates epidemiological, affective, and psychophysiological perspectives, with more precise language for describing stress measures. We articulate an integrative working model, highlighting how stressor exposures across the life course influence habitual responding and stress reactivity, and how health behaviors interact with stress. We offer a Stress Typology articulating timescales for stress measurement - acute, event-based, daily, and chronic - and more precise language for dimensions of stress measurement

A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation

Cutaneous sclerosis (CS) occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life

The Chromatin Remodelling Complex B-WICH Changes the Chromatin Structure and Recruits Histone Acetyl-Transferases to Active rRNA Genes

The chromatin remodelling complex B-WICH, which comprises the William syndrome transcription factor (WSTF), SNF2h, and nuclear myosin 1 (NM1), is involved in regulating rDNA transcription, and SiRNA silencing of WSTF leads to a reduced level of 45S pre-rRNA. The mechanism behind the action of B-WICH is unclear. Here, we show that the B-WICH complex affects the chromatin structure and that silencing of the WSTF protein results in a compaction of the chromatin structure over a 200 basepair region at the rRNA promoter. WSTF knock down does not show an effect on the binding of the rRNA-specific enhancer and chromatin protein UBF, which contributes to the chromatin structure at active genes. Instead, WSTF knock down results in a reduced level of acetylated H3-Ac, in particular H3K9-Ac, at the promoter and along the gene. The association of the histone acetyl-transferases PCAF, p300 and GCN5 with the promoter is reduced in WSTF knock down cells, whereas the association of the histone acetyl-transferase MOF is retained. A low level of H3-Ac was also found in growing cells, but here histone acetyl-transferases were present at the rDNA promoter. We propose that the B-WICH complex remodels the chromatin structure at actively transcribed rRNA genes, and this allows for the association of specific histone acetyl-transferases

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity:PanCareLIFE dataset

Genetic association studies suggest a genetic predisposi- tion for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase ( TPMT ) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross- sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnos- tic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes ( ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2 ) were genotyped. The genotype and phenotype data represent a resource for conducting meta- analyses to derive a more precise pooled estimate of the ef- fects of genes on the risk of hearing loss due to platinum treatment

Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment

Dimorfismo sexual en el comportamiento altruista de jóvenes colombianos: correlatos electrofisiológicos y endocrinos

La especie humana se caracteriza por un alto nivel de complejidad en sus interacciones y estructuras sociales. Para Dunbar (1998), esta fue la principal razón que podría explicar el crecimiento relativo del cerebro, principalmente el lóbulo frontal, en nuestra especie y otros primates no humanos afines filogenéticamente. Las explicaciones de este autor parten de que un entorno social complejo generaría una mayor exigencia cognitiva para los individuos, dado que, para lograr eficacia en sus interacciones, deben aumentar su capacidad para recordar y manipular información social, reconocer las jerarquías y roles, reconocer estados emocionales y anticipar intenciones de otros individuos, así como realizar comportamientos estratégicos como el engaño táctico y el establecimiento de alianzas.1a edició

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG